(1) Field of the Invention
This invention relates to a process for producing hydroxy lactone 3: 1R, 2R, 5R-2-hydroxy-6-oxo-7-oxabicyclo[3.2.1]-octane, in optically pure form, useful as a precursor for producing an ultraviolet radiation absorber and as an intermediate in synthesizing the C.sub.20 -C.sub.34 fragment of the immunoregulant FK-506 and analogs thereof.
(2) Brief Disclosures in the Art
The novel 23-membered tricyclo-macrolide FK-506 very recently isolated and characterized by Tanaka, Kuroda, and co-workers, see JACS, 109, pp. 5031, 1987, and EPO Publication No. 0,184,162, has been shown to possess exceptional immunosuppressive activity. The potential usefulness of such an agent in bone marrow and organ transplantations coupled with its unique structural features has prompted many in the field to initiate an effort towards the total synthesis of FK-506. A highly diastereoselective synthesis of a C.20-C.34 subunit A, in its correct absolute configuration, i.e., ##STR1## has already been achieved as reported by S. Mills, R. Desmond, R. A. Reamer, R. P. Volante and I. Shinkai in Tetrahedron Letters, 1988, 29, 281.
In the course of that work, the need was established for the optically pure form of 1R, 2R, 5R-2-hydroxy-6-oxo-7-oxabicyclo[3.2.1]-octane of the structure: ##STR2##
Although the racemic form was known (see the reference of Tanaka, H.; et al, J. Am. Chem. Soc., 1987, 109, 5031; also Grewe, R.; Heinke, A.; Sommer, C.; Chem Ber., 1956, 89, 1978-1988), no procedure for obtaining optically pure 3 was described.
What is needed is an overall general synthesis utilizing readily available starting materials which would allow the synthesis of the hydroxy lactone 3, 1R, 2R, 5R-2-hydroxy-6-oxo-7-oxabicyclo[3.2.1]-octane in its desired optically pure form.